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Wereport four fatal cases of amebic encephalitis in children caused by the free-living pathogenic ameba Balamuthia mandrillaris.The clinical course ranged from subacute to fulminant. Provisional diagnoses were made either shortly before death or postmortem by an indirect immunofluorescent antibody test. Although the four cases occurred in different geographic locations, their common features may have diagnostic value for recognizing future cases of amebic encephalitis. The cases occurred in children 2 to 7.5 years old who were ostensibly immunocompetent and of Hispanic ethnicity. Three of the four children developed hydrocephalus during their illness. Increased awareness and timely diagnosis of this disease entity might lead to earlier intervention with improved outcome.